Smoking is the leading cause of preventable deaths worldwide, and new therapies are needed to help smokers quit. Nicotine is the primary addictive component of tobacco smoke, therefore blocking the actions of nicotine is a logical strategy for developing smoking cessation treatments. Immunization is a novel approach to attenuate the effects of nicotine by targeting the drug rather than the brain. Vaccination against nicotine alters nicotine pharmacokinetics and nicotine self-administration, yet the efficacy of vaccination may be limited by variable serum antibody levels, a delay in achieving effective antibody titers, and a lack of control over antibody affinity. Passive immunization with a monoclonal antibody against nicotine may provide advantages over vaccination in treating nicotine dependence by allowing manipulation of antibody serum levels and antibody affinity. This proposal will examine the effects of a monoclonal antibody against nicotine on nicotine distribution to the brain in rats, nicotine self-administration, and its ability to precipitate nicotine withdrawal over a range of doses. These studies will clarify the mechanisms of action by which immunization attenuates nicotine's effects and the clinical utility of passive immunization. In the United States, 20-25% of the population are smokers, and the many severe health consequences due to smoking are widely known. Nicotine is the main addictive component of tobacco smoke. This proposal will examine the use of immunotherapy such as vaccination to block the effects of nicotine, and develop more treatments to help individuals stop smoking. [unreadable] [unreadable] [unreadable]